> Details

Narumi, Yoko; Aoki, Yoko; Niihori, Tetsuya; Neri, Giovanni; Cavé, Hélène; Verloes, Alain; Nava, Caroline; Kavamura, Maria Ines; Okamoto, Nobuhiko; Kurosawa, Kenji; Hennekam, Raoul C.M.; Wilson, Louise C.; Gillessen‐Kaesbach, Gabriele; Wieczorek, Dagmar; Lapunzina, Pablo; Ohashi, Hirofumi; Makita, Yoshio; Kondo, Ikuko; Tsuchiya, Shigeru; Ito, Etsuro; Sameshima, Kiyoko; Kato, Kumi; Kure, Shigeo; Matsubara, Yoichi

Molecular and clinical characterization of cardio‐facio‐cutaneous (CFC) syndrome: Overlapping clinical manifestations with Costello syndrome

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Molecular and clinical characterization of cardio‐facio‐cutaneous (CFC) syndrome: Overlapping clinical manifestations with Costello syndrome
  • Contributor: Narumi, Yoko; Aoki, Yoko; Niihori, Tetsuya; Neri, Giovanni; Cavé, Hélène; Verloes, Alain; Nava, Caroline; Kavamura, Maria Ines; Okamoto, Nobuhiko; Kurosawa, Kenji; Hennekam, Raoul C.M.; Wilson, Louise C.; Gillessen‐Kaesbach, Gabriele; Wieczorek, Dagmar; Lapunzina, Pablo; Ohashi, Hirofumi; Makita, Yoshio; Kondo, Ikuko; Tsuchiya, Shigeru; Ito, Etsuro; Sameshima, Kiyoko; Kato, Kumi; Kure, Shigeo; Matsubara, Yoichi
  • imprint: Wiley, 2007
  • Published in: American Journal of Medical Genetics Part A
  • Language: English
  • DOI: 10.1002/ajmg.a.31658
  • ISSN: 1552-4833; 1552-4825
  • Keywords: Genetics (clinical) ; Genetics
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Cardio‐facio‐cutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by heart defects, a distinctive facial appearance, ectodermal abnormalities and mental retardation. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are caused by mutations in two genes, <jats:italic>PTPN11</jats:italic> and <jats:italic>HRAS</jats:italic>, respectively. Recently, we identified mutations in <jats:italic>KRAS</jats:italic> and <jats:italic>BRAF</jats:italic> in 19 of 43 individuals with CFC syndrome, suggesting that dysregulation of the RAS/RAF/MEK/ERK pathway is a molecular basis for CFC syndrome. The purpose of this study was to perform comprehensive mutation analysis in 56 patients with CFC syndrome and to investigate genotype–phenotype correlation. We analyzed <jats:italic>KRAS</jats:italic>, <jats:italic>BRAF</jats:italic>, and <jats:italic>MAP2K1/2</jats:italic> (MEK1/2) in 13 new CFC patients and identified five <jats:italic>BRAF</jats:italic> and one <jats:italic>MAP2K1</jats:italic> mutations in nine patients. We detected one <jats:italic>MAP2K1</jats:italic> mutation in three patients and four new <jats:italic>MAP2K2</jats:italic> mutations in four patients out of 24 patients without <jats:italic>KRAS</jats:italic> or <jats:italic>BRAF</jats:italic> mutations in the previous study [Niihori et al., <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#bib14">2006</jats:ext-link>]. No mutations were identified in <jats:italic>MAPK3/1</jats:italic> (ERK1/2) in 21 patients without any mutations. In total, 35 of 56 (62.5%) patients with CFC syndrome had mutations (3 in <jats:italic>KRAS</jats:italic>, 24 in <jats:italic>BRAF</jats:italic>, and 8 in <jats:italic>MAP2K1/2</jats:italic>). No significant differences in clinical manifestations were found among 3 <jats:italic>KRAS</jats:italic>‐positive patients, 16 <jats:italic>BRAF</jats:italic>‐positive patients, and 6 <jats:italic>MAP2K1</jats:italic>/<jats:italic>2</jats:italic>‐positive patients. Wrinkled palms and soles, hyperpigmentation and joint hyperextension, which have been commonly reported in Costello syndrome but not in CFC syndrome, were observed in 30–40% of the mutation‐positive CFC patients, suggesting a significant clinical overlap between these two syndromes. © 2007 Wiley‐Liss, Inc.</jats:p>